Nevin Manimala

J Endod. 2024 Apr 6:S0099-2399(24)00226-7. doi: 10.1016/j.joen.2024.03.014. Online ahead of print.

ABSTRACT

INTRODUCTION: Pathological conditions such as internal root resorption (IRR) may complicate root canal filling. This study aimed to evaluate and compare the obturation quality by measuring the percentage of obturation volume (POV) in root canals with artificial IRR obturated with different materials and techniques using cone beam computed tomography (CBCT).

METHODS: Forty single canal extracted mandibular premolars were decoronated to standardize their length to 14mm. Following instrumentation, the roots were cut horizontally, and artificial IRR cavities were made at the level of 7mm from the apex. The root halves were joined using cyanoacrylate adhesive. The samples were randomly assigned to four groups (n = 10), and the canals were filled as follows: Single-cone technique (SC), bulk-fill Bio-C Sealer (BF), Bio-C Repair for the coronal and middle third (BCR) +cold lateral condensation technique (CLC) for the apical third and continuous wave compaction technique (CWC). The pre-and post-obturation volumes and the POV were measured in the total canal and for the apical, middle, and coronal thirds separately using CBCT and Mimics Medical software. The results were analyzed statistically using one-way ANOVA and Tukey HSD test, and statistical significance was set at p<0.05.

RESULTS: BF group resulted in significantly lower total, coronal, middle and apical POV values compared to SC, BCR+ CLC, and CWC groups (p < 0.05), respectively. Also, at the apical third, the BCR+ CLC group showed significantly lower POV than the SC and CWC groups (P<0.05), respectively. The intra-group comparison showed that BF and BCR+ CLC groups had a significantly lower POV in the apical third compared to the middle third (p<0.05). Conversely, the CWC group had a significantly higher apical POV than the middle third (p<0.05).

CONCLUSIONS: The maximum POV was obtained using the CWC technique, Bio-C Repair, and SC technique with Bio-C Sealer, making their application in IRR more preferable than the BF Bio-C Sealer.

PMID:38588977 | DOI:10.1016/j.joen.2024.03.014

Am J Pharm Educ. 2024 Apr 6:100698. doi: 10.1016/j.ajpe.2024.100698. Online ahead of print.

ABSTRACT

OBJECTIVE: One of the barriers that might prevent an underrepresented minority (URM) individual from pursuing a professional career in the United States is finances. The high disproportionate burden of student debt among URM students further perpetuates the racial wealth gap. Therefore, this study sought to evaluate the extent to which URM students’ personal finance perceptions, and current and projected student loan indebtedness, affect post-graduation career intentions.

METHODS: A cross-sectional analysis was conducted using data from 4 cohorts of pharmacy students using a survey from November 2, 2022 to February 1, 2023. The financial perception survey included subscales namely personal finance self-efficacy, debt influence and pressure, and risk mitigation and retirement. Descriptive statistics, simple logistic regression, and multivariate logistic regression analyses were conducted.

RESULTS: 93 students completed the survey and had a mean age of 28.1+5.3 years. Seventy-one percent of the respondents were female, and 67.7% had completed a 4-year bachelor’s degree. There was a significant association between age and the intention to pursue postgraduate training as well as a significant association between risk mitigation and retirement perceptions and intention to pursue postgraduate training after adjusting for other factors.

CONCLUSION: Among students from largely minority backgrounds, age and confidence in their ability to make wise investment decisions for retirement are associated with a greater likelihood of pursuing post-graduate training opportunities.

PMID:38588974 | DOI:10.1016/j.ajpe.2024.100698

Ann Vasc Surg. 2024 Apr 6:S0890-5096(24)00173-0. doi: 10.1016/j.avsg.2024.02.007. Online ahead of print.

ABSTRACT

BACKGROUND: We investigated the long-term safety and efficacy of anatomical and extra-anatomical bypass for the treatment of unilateral iliac artery disease.

METHODS: A systematic search on PubMed, Scopus and Web of science for articles published by June 2023 was performed. We implemented a two-stage individual participant data (IPD) meta-analysis and pooled survival probabilities using the multivariate methodology of DerSimonian and Laird. The primary endpoint was primary patency at five and ten years of follow-up.

RESULTS: Ten studies encompassing 1907 patients were included. The five- and ten-year pooled primary patency for anatomical bypass was 83.27% (95% CI:69.99- 99.07) and 77.30% (95% CI:60.32- 99.04), with a mean primary patency time representing the duration individuals remained event-free of 10.08 years (95% CI:8.05-10.97). The five- and ten-year pooled primary patency for extra-anatomical bypass was 77.02% (95% CI:66.79-88.80) and 68.54% (95% CI:53.32-88.09) with a mean primary patency time of 9.25 years, (95% CI:7.21-9.68). Upon two-stage IPD meta-analysis anatomical bypass displayed a decreased risk for loss of primary patency compared to extra-anatomical bypass, hazard ratio (HR) 0.51 (95% CI:0.30-0.85). The five- and ten-year secondary patency for anatomical bypass was 96.83% (95% CI:90.28-100) and 96.13% (95% CI:88.72.3-100). The five- and ten-year secondary patency for extra-anatomical bypass was 91.39% (95% CI:84.32-99.04) and 85.05% (95% CI:74.43-97.18), with non-statistically significant difference between the two groups. The five- and ten-year survival for patients undergoing anatomical bypass was 67.99% (95% CI:53.84-85.85) and 41.09% (95% CI:25.36-66.57). The five- and ten-year survival for extra-anatomical bypass was 70.67% (95% CI:56.76-87.98) and 34.85% (95% CI:19.76-61.44). The mean survival time was 6.92 years (95% CI:5.56-7.89) for the anatomical and 6.78 years (95% CI:5.31-7.63) for the extra-anatomical groups. The pooled overall thirty-day mortality was 2.32% (95% CI:1.12-3.87) with meta-regression analysis displaying a negative association between year of publication and mortality (β =-0.0065, p<0.01). Further analysis displayed a thirty-day mortality of 1.29% (95% CI:0.56-2.26) versus 4.02% (95% CI:1.78-7.03), (p=0.02) for studies published after and before the year 2000. Non-statistically significant differences were identified between the two groups concerning long-term and thirty-day mortality outcomes.

CONCLUSION: While we have demonstrated favorable long-term primary and secondary patency outcomes for both surgical techniques, anatomical bypass exhibited a reduced risk of primary patency loss potentially reflecting its inherent capacity to circumvent the anticipated disease progression in the distal aorta and the contralateral donor artery. The reduction in perioperative mortality observed in our review, coupled with the anachronistic demographic characteristics and inclusion criteria presented in the existing literature, underscores the imperative necessity for contemporary research.

PMID:38588957 | DOI:10.1016/j.avsg.2024.02.007

Am J Med. 2024 Apr 6:S0002-9343(24)00216-X. doi: 10.1016/j.amjmed.2024.04.007. Online ahead of print.

ABSTRACT

PURPOSE: Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures.

METHODS: Magnetic resonance spectroscopy (MRS) data was acquired with a 3T Prisma MRI scanner. We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n=17), ME/CFS (n=17), and healthy controls (n=10) using Osprey software. The statistical analyses were performed using SPSS version 29. Age and sex were included as nuisance covariates.

RESULTS: Glutamate levels were significantly higher in long COVID (p=0.02) and ME/CFS (p=0.017) than in healthy controls. No significant difference was found between the two patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (p=0.012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS.

CONCLUSION: Our study identified significantly elevated Glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the two patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.

PMID:38588934 | DOI:10.1016/j.amjmed.2024.04.007

Radiother Oncol. 2024 Apr 6:110271. doi: 10.1016/j.radonc.2024.110271. Online ahead of print.

ABSTRACT

PURPOSE: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities.

MATERIALS AND METHODS: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis.

RESULTS: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively).

CONCLUSIONS: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice.

PMID:38588920 | DOI:10.1016/j.radonc.2024.110271

Free Radic Biol Med. 2024 Apr 6:S0891-5849(24)00382-4. doi: 10.1016/j.freeradbiomed.2024.04.211. Online ahead of print.

ABSTRACT

DNA repair is essential to maintain genomic integrity and may affect colorectal cancer (CRC) patients’ risk of secondary cancers, treatment efficiency, and susceptibility to various comorbidities. Bioactive compounds identified in plant food have the potential to modulate DNA repair mechanisms, but there is limited evidence of how dietary factors may affect DNA repair activity in CRC patients in remission after surgery. The aim of this study was to investigate the effect of a 6 months personalized intensive dietary intervention on DNA repair activity in post-surgery CRC patients (stage I-III). The present study included patients from the randomized controlled trial CRC-NORDIET, enrolled 2-9 months after surgery. The intervention group received an intensive dietary intervention emphasizing a prudent diet with specific plant-based foods suggested to dampen inflammation and oxidative stress, while the control group received only standard care advice. The comet-based in vitro repair assay was applied to assess DNA repair activity, specifically base excision repair (BER), in peripheral blood mononuclear cells (PBMCs). Statistical analyses were conducted using gamma generalized linear mixed models (Gamma GLMM). A total of 138 CRC patients were included, 72 from the intervention group and 66 from the control group. The BER activity in the intervention group did not change significantly compared to the control group. Our findings revealed a substantial range in both inter- and intra-individual levels of BER. In conclusion, the results do not support an effect of dietary intervention on BER activity in post-surgery CRC patients during a 6-month intervention period.

PMID:38588903 | DOI:10.1016/j.freeradbiomed.2024.04.211

Mol Biochem Parasitol. 2024 Apr 6:111618. doi: 10.1016/j.molbiopara.2024.111618. Online ahead of print.

ABSTRACT

Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2.

PMID:38588892 | DOI:10.1016/j.molbiopara.2024.111618

J Foot Ankle Surg. 2024 Apr 6:S1067-2516(24)00068-1. doi: 10.1053/j.jfas.2024.03.003. Online ahead of print.

ABSTRACT

Residual osteomyelitis is a frequent problem following surgical intervention for diabetic foot infection. The current Infectious Disease Society of America guidelines recommend 4-6 weeks of initial intravenous antibiotics for treatment of residual osteomyelitis. However, recent literature suggests oral antibiotic therapy is not inferior to intravenous therapy. The primary aim of this study was to evaluate treatment success in 128 patients receiving oral versus intravenous antibiotics for residual osteomyelitis in the diabetic foot after amputation at a Level 1 academic medical trauma center. Treatment success was defined as completion of at least 4 weeks antibiotic therapy, complete surgical wound healing, and no residual infection requiring further debridement or amputation within one year of the initial surgery. Patients with peripheral arterial disease were excluded. A retrospective chart review was performed, and we found no statistically significant difference in treatment success between these two groups (p=0.2766). Median time to healing for oral antibiotic treatment was 3.17 months compared to 4.06 months for intravenous treatment (p=0.1045). Furthermore, there was no significant difference in group demographics or comorbidities, aside from more patients in the intravenous group having coronary artery disease (p=0.0416). Type of closure and type of microbial infection was also not associated with a difference in outcomes between the two treatment arms. The results of the present study suggest oral antibiotics for treatment of residual osteomyelitis are not inferior to intravenous therapy and may be more efficacious for certain patients regarding cost and ease of administration. LEVEL OF CLINICAL EVIDENCE: : 3.

PMID:38588891 | DOI:10.1053/j.jfas.2024.03.003

Mod Pathol. 2024 Apr 6:100485. doi: 10.1016/j.modpat.2024.100485. Online ahead of print.

ABSTRACT

Several studies have developed various artificial intelligence (AI) models for immunohistochemical analysis of programmed death ligand 1 (PD-L1) in patients with non-small cell lung carcinoma; however, none have focused on specific ways by which AI-assisted systems could help pathologists determine the tumor proportion score (TPS). Herein, we developed an AI model to calculate the TPS of the PD-L1 22C3 assay and evaluated whether and how this AI-assisted system could help pathologists determine the TPS and analyze how AI-assisted systems could affect pathologists’ assessment accuracy. We assessed the four methods of the AI-assisted system: 1) and 2) pathologists first assessed and then referred to automated AI scoring results (1, positive tumor cell percentage; 2, positive tumor cell percentage and visualized overlay image) for a final confirmation, and 3) and 4) pathologists referred to the automated AI scoring results (3, positive tumor cell percentage; 4, positive tumor cell percentage and visualized overlay image) while determining TPS. Mixed model analysis was used to calculate the odds ratios (ORs) with 95% confidence intervals for AI-assisted TPS 1) to 4) compared with pathologists’ scoring. For all 584 samples of tissue microarray, the OR for AI-assisted TPS 1) to 4) was 0.94-1.07 and not statistically significant. Of them, we found 332 cases of discordant cases, on which the pathologists’ judgments were inconsistent; the ORs for AI-assisted TPS 1), 2), 3), and 4) were 1.28 (1.06-1.54, p = 0.012), 1.29 (1.06-1.55, p = 0.010), 1.28 (1.06-1.54, p = 0.012), and 1.29 (1.06-1.55, p = 0.010), respectively, which were statistically significant. For discordant cases, the OR for each AI-assisted TPS compared with the others was 0.99-1.01 and not statistically significant. This study emphasized the usefulness of the AI-assisted system for cases wherein pathologists had difficulty determining the PD-L1 TPS.

PMID:38588885 | DOI:10.1016/j.modpat.2024.100485

Mod Pathol. 2024 Apr 6:100486. doi: 10.1016/j.modpat.2024.100486. Online ahead of print.

ABSTRACT

The role of Artificial intelligence (AI) in pathology is one that offers many exciting new possibilities for improving patient care. This study contributes to this development by identifying the viability of AICyte Assistive System for cervical screening, and to investigate the utility of the system in assisting with workflow and diagnostic capability. In this study, a novel scanner was developed using a Ruiqian WSI-2400, trademarked AICyte Assistive system, to create AI-generated gallery of the most diagnostically relevant images, objects of interest (OOI), and provide categorical assessment, according to Bethesda category, for cervical ThinPrep Pap slides. For validation purposes, two pathologists reviewed OOIs from 32,451 cases of ThinPrep Paps independently, and their interpretations were correlated with the original ThinPrep interpretations (OTPI). The analysis was focused on the comparison of reporting rates, correlation between cytological results and histological follow-up findings, and the assessment of independent AICyte screening utility. Pathologists using the AICyte system had a mean reading time of 55.14 seconds for the first 3,000 cases trending down to 12.90 seconds in the last 6,000 cases. Overall average reading time was 22.23 seconds per case as compared to a manual reading time approximation of 180 seconds. Usage of AICyte compared to OTPI had similar sensitivity (97.89% vs 97.89%) and a statistically significant increase in specificity (16.19% vs 6.77%). When AICyte was run alone at a 50% negative cut-off value, it was able to read slides with a sensitivity of 99.30% and specificity of 9.87%. When AICyte was run independently at this cut-off value, no sole case of HSIL/SCC squamous lesion was missed. AICyte can provide a potential tool to help pathologists in both diagnostic capability and efficiency, which remained reliable as compared to baseline standard. Also unique for AICyte is the development of a negative cutoff value for which AICyte can categorize cases as “not needed for review” to triage cases and lower pathologist workload. This is the largest case number study that pathologists reviewed OOI with AI assistive system. The study demonstrates that AI assistive system can be broadly applied for cervical cancer screening.

PMID:38588882 | DOI:10.1016/j.modpat.2024.100486